Temporary Focal Cerebral Ischemia Research Articles

Reduction of Vasogenic Edema and Infarction by MK-801 in Rats after Temporary Focal Cerebral Ischemia

Reduction of Vasogenic Edema and Infarction by MK-801 in Rats after Temporary Focal Cerebral Ischemia

Endogenous opioid system activity following temporary focal cerebral ischemia.

We studied changes in opioid receptors (mu, delta, kappa) concentrations during temporary middle cerebral artery occlusion (MCAO) in cats by sequential displacement of unselective opioid antagonist, [3H]-diprenorphine with highly selective ligands for mu, delta and kappa, subsites. Following threshold cerebral ischemia (rCBF < 10 ml/100 g/min) there was a 2 to 3 fold increase in the 3 opioid receptor subtype concentrations at 10 min following the release of MCAO. Further, 56% of the cats depicted early postischemic hyperemia BBB opening, at 1 h and 3 h following the release of occlusion, with significant subsequent progression of brain edema. We believe that the enhanced brain opioid activity may be relevant to the neuronal damage caused by the early postischemic BBB opening.

Brain eicosanoid levels during temporary focal cerebral ischemia in rats: a microdialysis study.

After transient cerebral ischemia, the brain is vulnerable to additional injury via hypoperfusion deficits. Eicosanoids with vasoconstrictor properties, such as thromboxane A2 (TxA2), may worsen postischemic hypoperfusion. The effect of temporary middle cerebral artery occlusion (MCAo) on brain TxB2 (the stable metabolite of TxA2) was evaluated in isoflurane-anesthetized rats. Microdialysis probes were placed in the caudate nucleus and temporal cortex. Each rat underwent one of the following ischemic regimens: groups I, II, and III--MCAo was maintained for 60, 120, and 180 min, respectively, followed by 120 min of reperfusion; group IV--a sham group in which MCAo and reperfusion were simulated; group V--7 h of MCAo only. Dialysate was measured for TxB2 by radioimmunoassay. Brain levels of TxB2 did not deviate from baseline during MCAo (or in the sham group). In contrast, during reperfusion, there was a significant increase in TxB2 following 180 min of MCAo but not after 60 or 120 min or MCAo (p < 0.05). These data indicate that, in this model of cerebral ischemia, TxB2 does not increase during MCAo. However, following a threshold duration of MCAo (180 min), the vasoconstrictor TxB2 may modulate postischemic hypoperfusion. These findings may have implications in the pharmacologic treatment of postischemic hypoperfusion and reperfusion brain injury.

Effects of ketamine on outcome from temporary middle cerebral artery occlusion in the spontaneously hypertensive rat

This experiment evaluated the potential for ketamine HCl, a non-competitive glutamate antagonist, to minimize injury resulting from temporary focal cerebral ischemia. Male spontaneously hypertensive rats were randomly assigned to receive either ketamine ( n = 13) or halo hane anesthesia ( n = 12) during 2 h reversible middle cerebral artery occlusion (MCAO). Ketamine was administered as a 50 mg/kg i.v. loading dose followed by a continous 1.25 mg/kg/min i.v. infusion beginning 25 min prior to ischemia and continued until 30 min after reperfusion. An additional group of rats (ketamine-shmas, n = 8) underwent craniectomy and ketamine administration (as above) but the middle cerebral artery was not ligated. Physiologic values were similar between groups with the exception of plasma glucose which was elevated in the halothane-MCAO group. After 4 days recovery. rats in all groups were neurologically evaluated. There were no differences between the two groups undergoing MCAO for neurologic grading or open field behavior, although both groups performed worse than did ketamine-shams ( P < 0.05). In contrast, motor performance revealed more severe deficits in the ketamine-MCAO rats vs either the halothane-MCAO or ketamine-sham groups ( P < 0.05). Cerebral infare volume was then planimetrically measured after triphenyl tetrazolium chloride (TTC) stining of fresh brain sections. Mean ± S.D. infarct volume was not different between the halothane-MCAO (134 ± 51 mm 3) and ketamine-MCAO (131 ± 64 mm 3) groups. Seven of 8 sham rats were free of TTC demarcated injury and in the remaining rat injury was minimal. These results indicate that under conditions of reversible focal ischemia, pretreatment with ketamine HCl offers no protective benefit over halothane anesthesia.

Nitrous Oxide Does Not Alter Infarct Volume in Rats Undergoing Reversible Middle Cerebral Artery Occlusion

This experiment was designed to determine if nitrous oxide alters neurologic and pathologic outcome from temporary focal cerebral ischemia in spontaneously hypertensive rats deeply anesthetized with a barbiturate. Two groups of rats were given intravenous methohexital such that a stable EEG pattern of burst suppression was achieved. In one group of rats (n = 11), the lungs were mechanically ventilated with 70% N2O/30% O2, and in the other group (n = 10), ventilation was done with 70% nitrogen/30% O2. The middle cerebral artery was then occluded for 2 h, during which time mean arterial pressure, blood gases, hematocrit, plasma glucose, and head temperature were held constant between groups. The total doses of methohexital administered were similar in both groups as were the plasma methohexital concentrations immediately prior to onset of ischemia. After reperfusion of the middle cerebral artery, the animals were allowed to awaken. Neurologic evaluations were performed prior to ischemia and at 24 and 96 h postischemia. Cerebral infarct volume was measured at 96 h postischemia using triphenyl tetrazolium chloride staining and computer imaging techniques. There were no neurologic differences between the N2O and nitrogen groups at any experimental interval although both groups exhibited deficits at both 24 and 96 h postischemia relative to preischemic values. The two groups also had nearly identical cerebral infarct volumes (N2O = 231 +/- 97 mm3; nitrogen = 226 +/- 75 mm3; mean +/- SD).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the Effects of Isoflurane and Thiopental on Neurologic Outcome and Neuropathology After Temporary Focal Cerebral Ischemia in Primates

Anesthesia Research Laboratories, Department of Anesthesiology, Mayo Foundation and Mayo Clinic, Rochester, Minnesota

Nonhyperemic blood flow restoration and brain edema in experimental focal cerebral ischemia.

The effect of suppression of postischemic reactive hyperemia on the blood-brain barrier (BBB) and ischemic brain edema after temporary focal cerebral ischemia was studied in cats under ketamine and alpha-chloralose anesthesia. Regional cerebral blood flow (rCBF) was measured by a thermal diffusion method and a hydrogen clearance method. The animals were separated into three groups. In Group A, the left middle cerebral artery (MCA) was occluded for 6 hours. In Group B, the MCA was occluded for 3 hours and then reperfused for 3 hours; postischemic hyperemia was suppressed to the preischemic level by regulating the degree of MCA constriction. In Group C, the MCA was occluded for 3 hours and reperfused for 3 hours without suppressing the postischemic reactive hyperemia. The brain was removed and cut coronally at the site of rCBF measurement. The degree of ischemic edema was assessed by gravimetry in samples taken from the coronal section and correlated with the degree of BBB disruption at the corresponding sites, evaluated by densitometric determination of Evans blue discoloration. The findings showed that 1) ischemic edema was significantly exacerbated by postischemic hyperemia during reperfusion in parallel with the degree of BBB opening to serum proteins, and 2) suppression of postischemic hyperemia significantly reduced the exacerbation of ischemic edema and BBB opening. These findings indicate that blood flow may be restored without significant exacerbation of postischemic edema by the suppression of postischemic hyperemia in focal cerebral ischemia.

Computerized cortical surface electroencephalography after temporary middle cerebral artery occlusion in rabbits.

The sensitivity and regional specificity of intraoperative electroencephalographic (EEG) monitoring in cerebral ischemia was evaluated in a new experimental model of temporary focal cerebral ischemia in rabbits. EEG potentials were recorded directly from the cortical surface using a bipolar disc electrode grid and were analyzed by computer. Groups of 5 animals each underwent temporary occlusion of the left middle cerebral arterial trunk for 5, 10, 20, 30, 45, or 60 minutes. EEG data were recorded from the cortex proximal (temporal site) and distal (parasagittal site) to the middle cerebral arterial trunk during occlusion and 2 hours of reperfusion. EEG suppression was detected immediately after occlusion at the temporal site by analysis of power spectra in 29 of 30 rabbits (mean power, 32% of base line), by compressed spectral array (CSA) edge analysis in 23, and by analysis of the conventional EEG wave form in 24. Within 5 minutes after the start of occlusion, all 30 rabbits showed EEG power suppression and 26 showed decrease in the CSA edge frequency or in the routine EEG wave form. By the end of the occlusion period, EEG power at the temporal site had decreased to 20.5% of base line. At the parasagittal site, a lesser degree of EEG suppression was detected; 20 rabbits had an initial loss of EEG power (mean, 85.7% of base line), 13 had decrease in the CSA edge, and 7 had suppression of the EEG wave form. By the end of the occlusion period, spectral power at the parasagittal site had decreased in 25 of 30 rabbits to a mean of 86.9% of base line.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Fluosol on oxygen availability, regional cerebral blood flow, and infarct size in a model of temporary focal cerebral ischemia.

Twenty-four cats had an intravenous infusion of either Fluosol or saline and then were subjected to 2 hours of middle cerebral artery occlusion. All the animals infused with Fluosol and one-half the animals infused with saline were ventilated with 100% O2. Tissue oxygen availability and regional cerebral blood flow were measured by platinum electrodes using direct voltage recordings for oxygen measurements and hydrogen clearance curves for measurements of cerebral blood flow. With 100% oxygenation tissue oxygen availability increased significantly in the Fluosol treated animals, however, during the time of ischemia oxygen availability decreased below baseline values to about an equal level whether the animals were treated with Fluosol or saline. Regional cerebral blood flow fell to a similar value in all groups during the time of occlusion. One hour after reperfusion blood flow increased considerably above baseline values in all groups and oxygen availability also increased in all groups but particularly in the Fluosol treated animals. Overall mortality and the size of infarction 1 week after the ischemic insult were not significantly different in the three groups. Mortality was directly related to the size of the infarct which, in turn, was related to the degree of ischemia during the time of occlusion.

Neurologic deficit, blood flow and biochemical sequelae of reversible focal cerebral ischemia in cats

Temporary focal cerebral ischemia was induced in 23 cats by occluding the left middle cerebral artery (MCA) for 2 h. Animals then were divided into groups for unforced reperfusion of varying duration ranging from 2 to 48 h. Regional blood flow (rCBF) at the borders of the ischemic area was measured repeatedly using the hydrogen clearance technique, and neurological ratings were obtained, both during ischemia and reperfusion. At the scheduled end of reperfusion brains were frozen in situ with liquid nitrogen, and regional distributions of biochemical substrate contents as well as tissue pH were visualized using bioluminescence and fluorescence techniques. During focal ischemia collateral flow in the border zone dropped to 55 ± 20.3% of control level, and all animals developed a neurologic deficit with a median of 6 points on a disability scale from 0 to 10, rCBF and functional impairment being closely correlated ( τ = −0.47, P 1 < 0.005). After reopening of the MCA there was an immediate and rather uniform increase in border zone flow to 105 ± 25.7% of control level, while neurologic recovery was quite variable. In all but one animal reversible ischemia led to persistent disturbances in the energy-producing metabolism as demonstrated by the low regional ATP content, which in part was accompanied by a diminished NADH fluorescence and an alkaline pH shift at high tissue glucose levels. These findings suggest that disturbances in cerebral energy metabolism induced by temporary ischemia may be caused by inhibition of the glycolytic pathway that is hardly reversed by unforced reperfusion and, therefore, results in permanent damage.

VASOSPASM AND FOCAL CEREBRAL ISCHEMIA

The present article deals with the vasoconstrictions that can be produced in the pial arterial vessels of animals by electrical and mechanical stimulation. The purpose of the investigation was mainly to determine, if possible, a method of producing temporary focal cerebral ischemia. Since the middle of the last century many observers have suggested that such ischemia might be the causative factor in epilepsy, migraine, temporary hemiplegias, hypesthesias, aphasias and other transitory neurologic phenomena. No one, however, as far as I know, has produced and studied the effect on the brain of temporary focal cerebral ischemia. In this paper a method is described whereby temporary focal cerebral ischemia may be produced. Such ischemia did not cause any clinical epileptiform manifestations in unanesthetized cats so long as the motor gyrus was not involved in the ischemia. That subclinical epileptiform neuronal activity might have occurred as a result of the ischemia cannot be